Effects of Zolpidem Extended-Release on Withdrawal and Sleep in Cannabis Users

描述（由申请人提供）：自20世纪90年代中期以来，因大麻相关问题接受治疗的人数增加了一倍多。临床试验表明，接受大麻问题治疗的大多数人都复发了，复发率与观察到的其他滥用药物的复发率相当。目前还没有公认的治疗大麻依赖的药物疗法。在之前的研究中，屈大麻酚（Marinol）显示出治疗大麻依赖的潜力，但这些研究涉及每天服用3-5次屈大麻酚，这引起了一些关于认知和精神运动能力、药物依从性和转移潜力的潜在损害的担忧。本提案将通过检查睡前服用唑吡坦缓释剂（Ambien CR(r)）对大麻戒断严重程度、客观睡眠测量和副作用的影响，扩展先前治疗大麻使用障碍的药物开发研究。选择这种药物进行研究是因为它已被证明可以逆转睡眠问题，这是大麻戒断的一个突出症状，睡眠研究表明，睡眠功能障碍的改善可能会导致其他大麻戒断效应的减弱，如焦虑、抑郁和愤怒。这方面的研究也很有吸引力，因为唑吡坦和其他几种睡眠药物据称与曲大麻酚相比副作用更小，滥用风险也更小，然而，这些影响尚未在大麻使用者的对照研究中得到评估。拟议的实验将仔细研究唑吡坦（12.5毫克）和安慰剂对每日大麻使用者在短暂的突然戒断大麻期间的影响。使用受试者内交叉设计，参与者将依次完成基线随意吸食大麻，药物治疗后突然戒断大麻，并在下一个戒断期之前返回基线。在研究的每个阶段，每天都将评估大麻戒断严重程度、睡眠多导睡眠图（PSG）、在一系列最先进的认知和精神运动测试中的表现，以及对药物副作用的主观评分。本实验的结果将提供初步信息，了解已知的改善睡眠功能的药物是否安全有效地替代曲大麻酚作为治疗大麻依赖的药物疗法，并将提供关于慢性大麻使用和戒断对睡眠结构影响的新数据。

DESCRIPTION (provided by applicant): Treatment admissions for cannabis-related problems have more than doubled since the mid 1990's. Clinical trials indicate that a majority of those who enter treatment for cannabis problems relapse, and relapse rates are comparable to those observed for other drugs of abuse. Currently there are no accepted pharmacotherapies for treating cannabis dependence. Dronabinol (Marinol(r)) has exhibited effects in prior studies suggesting potential for treating cannabis dependence, but these studies involved dronabinol administration 3-5 times per day, which raises some concerns with regards to potential impairment of cognitive and psychomotor abilities, medication adherance, and potential for diversion. The present proposal will extend previous research on medications development for the treatment of cannabis use disorders by examining the effects of zolpidem extended-release (Ambien CR(r)) administered at bedtime on cannabis withdrawal severity, objective sleep measures, and presence of side-effects. This medication was selected for study because it has been demonstrated to reverse sleep problems, a prominent symptom of cannabis withdrawal, and sleep research suggests that it is possible that amelioration of sleep dysfunction may result in an attenuation of other cannabis withdrawal effects such as anxiety, depression, and anger. This line of research is also attractive because zolpidem and several other sleep medications are purported to have fewer side effects and less abuse liability compared with dronabinol, however, these effects have not been assessed in controlled studies of cannabis users. The proposed experiment will carefully study the effects of zolpidem (12.5mg) and placebo in daily cannabis users during brief periods of abrupt cannabis abstinence. Using a within-subjects crossover design, participants will sequentially complete periods of baseline ad-libitum cannabis smoking, abrupt cannabis abstinence with medication, and a return to baseline prior to the next abstinence period. Cannabis withdrawal severity, sleep polysomnography (PSG), performance on a comprehensive battery of state-of-the-art cognitive and psychomotor tests, and subjective ratings of medication side effects will be assessed daily in each phase of the study. Outcomes from this experiment will provide initial information regarding whether medications known to improve sleep function are safe and effective alternatives to dronabinol for use as pharmacotherapies in the treatment of cannabis dependence, and will provide new data regarding the effects of chronic cannabis use and withdrawal on sleep architecture. PUBLIC HEALTH RELEVEANCE: The number of people seeking treatment for marijuana-related problems is on the rise, yet there is no currently accepted medication proven to help them quit. This research is designed to investigate the ability of the FDA approved sleep medication zolpidem extended-release (Ambien CR(r)) to reduce the withdrawal effects associated with stopping daily marijuana use, and to carefully study the effects of quitting marijuana on sleep functioning and the occurance of safety risks and side-effects associated with the medication in marijuana users.